Dose escalation of biologics in Crohn's disease: critical review of observational studies

Curr Med Res Opin. 2017 Aug;33(8):1433-1449. doi: 10.1080/03007995.2017.1335001. Epub 2017 Jun 11.

Abstract

Background: Biologics used to treat Crohn's disease (CD) may lose their effect over time, requiring dose escalation. Little information is available on this topic.

Aim: To summarize rates of dose escalation, duration, de-escalation in observational studies of CD in adults treated with adalimumab, infliximab, and vedolizumab in Europe.

Methods: Two independent investigators searched Medline and Embase for observational studies published in 1998-2015 and proceedings from four major scientific meetings. Rates were summarized descriptively.

Results: In total, 58 articles from 12 European countries were analyzed (49 full articles, nine abstracts), providing 65 reports with 7,850 patients; 35 reported on 3,830 patients with adalimumab (ADA), and 30 on 4,020 patients with infliximab (IFX). Overall, 29.9% ± 3.5% of patients required dose escalation; 32.8% ± 6.2% with ADA and 25.2% ± 2.4% with IFX (p = .35 between drugs). Rates increased according to line of treatment: 19% for first line, 37% second, and 41% third. The median time to loss of response was 12 months, and the weighted average was 15.1 ± 5.9 months. Median time to escalation was 6.7 months; 6.7 months for ADA and 7.5 for IFX (p = .86). Short-term response rates to escalation were 63% for ADA and 45% for IFX (p = .08). There were no papers available for vedolizumab.

Conclusions: A substantial proportion of patients receiving ADA or IFX for Crohn's disease require dose escalation after a short period of time.

Keywords: Crohn’s disease; adalimumab; biologics; dose escalation; infliximab.

Publication types

  • Review

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / therapeutic use
  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biological Products / administration & dosage*
  • Biological Products / therapeutic use
  • Crohn Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Europe
  • Humans
  • Infliximab / administration & dosage
  • Infliximab / therapeutic use
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Biological Products
  • vedolizumab
  • Infliximab
  • Adalimumab